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To investigate the relationship between serum levels of the neuroaxonal degeneration biomarker neurofilament light chain (NFL) and phenotype in ALS. Serum NFL (sNFL) concentration was quantified in 209 ALS patients and 46 neurologically healthy controls (NHCs). sNFL was clearly increased in ALS patients and discriminated them from NHCs with AUC = 0.9694. Among ALS patients, females had higher sNFL levels, especially in case of bulbar onset. sNFL was more increased in phenotypes with both upper (UMN) and lower motor neuron (LMN) signs, and particularly in those with UMN predominance, compared to LMN forms. At the same time, primary lateral sclerosis (PLS) had significantly lower levels compared to UMN-predominant ALS (AUC = 0.7667). sNFL correlated negatively with disease duration at sampling and ALSFRS-R score, positively with disease progression rate, differed among King's stages, and was negatively associated with survival. It also correlated with clinical/neurophysiological indices of UMN and LMN dysfunction (Penn UMN Score, LMN score, MRC composite score, active spinal denervation score). On the contrary, sNFL was not associated with cognitive deficits nor with respiratory parameters. Notably, we found a negative correlation between sNFL and estimated glomerular filtration rate (eGFR). We confirm that ALS is characterized by increased sNFL levels, whose main determinant is the rate of degeneration of both UMNs and LMNs. sNFL is a biomarker of only motor, not of extra-motor, disease. The negative correlation with kidney function might reflect varying renal clearance of the molecule and deserves further investigation before introducing sNFL measurement as routine test in clinical care of ALS patients.

Objective To compare serum levels of the astrocyte biomarker glial fibrillary acidic protein (GFAP) in patients with amyotrophic lateral sclerosis (ALS) and neurologically healthy controls and to analyze the relations between serum GFAP (sGFAP) and phenotype in ALS. Methods We studied 114 ALS patients and 38 controls. sGFAP was quantified with single molecule array (Simoa) technology. Results In both ALS patients and controls, sGFAP moderately correlated with age. ALS patients had higher sGFAP levels compared to controls, but this yielded a weak discriminative performance (AUC = 0.6198). In ALS, sGFAP was not associated with most of the motor phenotypic features, including site of onset, functional status, disease progression rate, disease stage, and indices of upper (UMN) and lower motor neuron (LMN) impairment. However, sGFAP negatively correlated with cognitive scores regarding ALS‐nonspecific functions, particularly memory (r = −0.2082) and tended to be higher in ALS patients with eye movement abnormalities (p = 0.0628). sGFAP also correlated with polysomnographic indices of oxygen desaturation (ODI; r = 0.2639) and apnea‐hypopnea (AHI; r = 0.2858). In a multivariate analysis, sGFAP was negatively associated with survival (HR = 1.005). Relevantly, we found a negative correlation between sGFAP and estimated glomerular filtration rate (eGFR; r = −0.3500). Interpretation Our work provides neurochemical evidence of astrocyte involvement in ALS pathophysiology and particularly in the development of extra‐motor manifestations (namely, cognitive – memory – impairment) and respiratory dysfunction. The negative correlation between sGFAP and eGFR has practical relevance and should not be disregarded in future investigations.

Background This study aimed at assessing the cross-sectional and longitudinal clinimetrics and feasibility of the Frontal Assessment Battery (FAB) in non-demented Parkinson’s disease (PD) patients. Methods N  = 109 PD patients underwent the FAB and the Montreal Cognitive Assessment (MoCA). A subsample of patients further underwent a thorough motor, functional and behavioral evaluation (the last including measures of anxiety, depression and apathy). A further subsample was administered a second-level cognitive battery tapping on attention, executive functioning, language, memory, praxis and visuo-spatial abilities. The following properties of the FAB were tested: (1) concurrent validity and diagnostics against the MoCA; (2) convergent validity against the second-level cognitive battery; (4) association with motor, functional and behavioral measures; (5) capability to discriminate patients from healthy controls (HCs; N  = 96); (6) assessing its test–retest reliability, susceptibility to practice effects and predictive validity against the MoCA, as well as deriving reliable change indices (RCIs) for it, at a ≈ 6-month interval, within a subsample of patients ( N  = 33). Results The FAB predicted MoCA scores at both T0 and T1, converged with the vast majority of second-level cognitive measures and was associated with functional independence and apathy. It accurately identified cognitive impairment (i.e., a below-cut-off MoCA score) in patients, also discriminating patients from HCs. The FAB was reliable at retest and free of practice effects; RCIs were derived according to a standardized regression-based approach. Discussion The FAB is a clinimetrically sound and feasible screener for detecting dysexecutive-based cognitive impairment in non-demented PD patients.

The gene is an established susceptibility locus for amyotrophic lateral sclerosis (ALS) and a determinant of shorter survival after disease onset, with up to 33.0 months difference in life expectancy for carriers of the rs12608932 risk genotype. However, its overall effect on other clinical features and ALS phenotypic variability is controversial. Genotype data of the rs12608932 SNP (A-major allele; C-minor allele) was obtained from a cohort of 972 ALS patients. Demographic and clinical variables were collected, including cognitive and behavioral profiles, evaluated through the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) - Italian version and the Frontal Behavioral Inventory (FBI); upper and lower motor neuron involvement, assessed by the Penn Upper Motor Neuron Score (PUMNS) and the Lower Motor Neuron Score (LMNS)/Medical Research Council (MRC) scores, respectively; the ALS Functional Rating Scale Revised (ALSFRS-R) score at evaluation and progression rate; age and site of onset; survival. The comparison between the three rs12608932 genotypes (AA, AC, and CC) was performed using the additive, dominant, and recessive genetic models. The rs12608932 minor allele frequency was 0.31 in our ALS cohort, in comparison to 0.33-0.41 reported in other Caucasian ALS populations. Carriers of at least one minor C allele (AC + CC genotypes) had a shorter median survival than patients with the wild-type AA genotype (-11.7 months, = 0.013), even after adjusting for age and site of onset, mutational status and gender. Patients harboring at least one major A allele (AA + AC genotypes) and particularly those with the wild-type AA genotype showed a significantly higher PUMNS compared to CC carriers ( = 0.015 and = 0.037, respectively), thus indicating a more severe upper motor neuron involvement. Our analysis did not detect significant associations with all the other clinical parameters considered. Overall, our findings confirm the role of as a determinant of survival in ALS patients and show the association of this locus also with upper motor neuron involvement.

Background . The present study aimed at deriving regression-based reliable change indices (RCIs) for the Montreal Cognitive Assessment (MoCA) in an Italian cohort of non-demented Parkinson’s disease (PD) patients. Methods N  = 33 consecutive, non-demented PD patients were followed-up at a 5-to-8-month interval ( M  = 6.6; SD  = 0.6) with the MoCA. Practice effects and test-retest reliability were assessed via dependent-sample t -tests and intra-class correlation (ICC) coefficients, respectively. RCIs were derived separately for raw and demographically adjusted MoCA scores according to a standardized regression-based approach by accounting for both baseline confounders (i.e., demographics, disease duration and Unified Parkinson’s Disease Rating Scale scores) and retest interval. Results No practice effects were found ( t (32) = 0.29; p  = .778), with acceptable test-retest reliability being detected (ICC = 0.67). MoCA scores at T0 proved to be the only significant predictor of T1 MoCA performances within both the model addressing raw scores and that addressing adjusted scores ( p s < 0.001). Conclusions The present study provides Italian practitioners and researchers with regression-based RCIs for the MoCA in non-demented PD patients, which can be reliably adopted for retest interval ≥ 5 and ≤ 8 months without encountering any practice effect.

Introduction Amyotrophic lateral sclerosis (ALS) individuals carrying the hexanucleotide repeat expansion (HRE) in the C9orf72 gene (C9Pos) have been described as presenting distinct features compared to the general ALS population (C9Neg). We aim to identify the phenotypic traits more closely associated with the HRE and analyse the role of the repeat length as a modifier factor. Methods We studied a cohort of 960 ALS patients (101 familial and 859 sporadic cases). Motor phenotype was determined using the MRC scale, the lower motor neuron score (LMNS) and the Penn upper motor neuron score (PUMNS). Neuropsychological profile was studied using the Italian version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS), the Frontal Behavioral Inventory (FBI), the Beck Depression Inventory-II (BDI-II) and the State-Trait Anxiety Inventory (STAI). A two-step PCR protocol and Southern blotting were performed to determine the presence and the size of C9orf72 HRE, respectively. Results C9orf72 HRE was detected in 55/960 ALS patients. C9Pos patients showed a younger onset, higher odds of bulbar onset, increased burden of UMN signs, reduced survival and higher frequency of concurrent dementia. We found an inverse correlation between the HRE length and the performance at ECAS ALS-specific tasks ( P  = 0.031). Patients also showed higher burden of behavioural disinhibition ( P  = 1.6 × 10 –4 ), lower degrees of depression ( P  = 0.015) and anxiety ( P  = 0.008) compared to C9Neg cases. Conclusions Our study provides an extensive characterization of motor, cognitive and behavioural features of C9orf72 -related ALS, indicating that the C9orf72 HRE size may represent a modifier of the cognitive phenotype.

Background This study is aimed at assessing the clinimetric properties and feasibility of the Italian version of the Montreal Cognitive Assessment (MoCA) in patients with Huntington’s disease (HD). Methods N  = 39 motor-manifest HD patients, N  = 74 Parkinson’s disease (PD) patients and N  = 92 matched HCs were administered the MoCA. HD patients further underwent the Unified Huntington’s Disease Rating Scale (UHDRS), self-report questionnaires for anxiety and depression and a battery of first- and second-level cognitive tests. Construct validity was tested against cognitive and behavioural/psychiatric measures, whereas ecological validity against motor-functional subscales of the UHDRS. Sensitivity to disease severity was tested, via a logistic regression, by exploring whether the MoCA discriminated between patients in Shoulson-Fahn stage ≤ 2 vs.  > 2. The same analysis was employed to test its ability to discriminate HD patients from HCs and PD patients. Results The MoCA converged towards cognitive and behavioural measures but diverged from psychiatric ones, being also associated with motor/functional measures from the UHDRS. In identifying patients with cognitive impairment, adjusted MoCA scores were highly accurate (AUC = .92), yielding optimal diagnostics at the cut-off of < 19.945 ( J  = .78). The MoCA was able to discriminate patients in the middle-to-advanced from those in the early-to-middle stages of the disease ( p  = .037), as well as to differentiate HD patients from both HCs ( p  < .001) and PD patients ( p  < .001). Conclusions The MoCA is a valid, diagnostically sound and feasible cognitive screener in motor-manifest HD patients, whose adoption is thus encouraged in clinical practice and research.

In this contribution, the tests of the pre-series gyrotron TH1509UA for the Divertor Tokamak Test facility (DTT) at the FALCON test facility are presented. This versatile test bed proves useful for testing continuous wave (CW) high-power gyrotrons, but also serves as a platform for testing components for the transmission line or the Upper Launcher of ITER and DTT. The gyrotron has demonstrated a power level of 1.02 MW at the gyrotron output window, corresponding to 980 kW at the output of the Matching Optics Unit (MOU) with a power variation during the pulse of < 2% after a stabilisation period. Additionally, an efficiency of 40% has been demonstrated during five consecutive 100 s pulses. Compared to the previous version, TH1509U, this gyrotron demonstrates the successful prevention of parasitic mode excitation over a wide range of parameters around the design operating point. The potential for even higher power performance has been shown in short pulses but not explored in long pulses yet, which instead focused on demonstrating compliance with the required specifications for the DTT project.